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EASL 2018 FRI-325
Efficacy and safety of combination therapy with interferon and
immunomodulators in entecavir-suppressed chronic hepatitis B
patients (the endeavor study)
D. Wu1, P. Wang1, M. Han1, Y. Chen2, X.-Y. Chen3, Q. Xia4, C. Zhu5,
Q. Xie6, J. Jiang7, L.Wei8, D. Tan9, X. Dou10, Y.-Y. Yu11, J. Hou11, Q. Ning1.
1Tongji Hospital, Tongji Medical College, Huazhong University of Science
and Technology, Department and Institute of Infectious Disease; 2The
First Affiliated Hospital of Wenzhou Medical University, China; 3Beijing
You’an Hospital, Capital Medical University, China; 4The First Affiliated
Hospital, School of Medicine, Zhejiang University; 5Jiangsu Province
Hospital; 6Shanghai Ruijin Hospital, Jiaotong University School of
Medicine; 7First Affiliated Hospital of Fujian Medical University; 8Peking
University People’s Hospital, China; 9Xiangya Hospital, Central South
University; 10Shengjing Hospital of China Medical University, China;
11Nanfang Hospital, Southern Medical University, China
Email: [email protected]
Background and Aims: The ideal endpoint for anti-HBV therapy is
the loss of hepatitis B surface antigen (HBsAg). The purpose of the
study was to determine the efficacy and safety of sequential
combination therapy with interferon (IFN), recombinant human IL-
2 (rhIL-2) and therapeutic vaccine in patients treated with long-term
entecavir (ETV).
Method: In this pilot and proof of concept, multicentre and
randomized trial, 94 HBeAg positive chronic hepatitis B patients
who had received ETV for at least 1 years, with HBV DNA ≤ 1000
copies/ml and hepatitis B e antigen (HBeAg) loss, were randomly
assigned (1:1:1) to receive ETV (0.5 mg/day, oral) for 48 weeks
(Group I) or IFN-α-2b (600 wIU every other day, subcutaneous) for 48
weeks (Group II) or IFN-α-2b for 48weeks in combination with rhIL-2
(25 wIU every other day, subcutaneous) for 12 weeks plus vaccine
(60ug/month, intramuscular) for 48 weeks (Group III). The primary
endpoint was HBsAg loss at week 48 (ClinicalTrials.gov:
NCT02360592). Peripheral immune cells were evaluated
dynamically.
Results: 94 patients were randomized; 93 received ≧ 1 study drug
dose. One patient whowere HBeAg-positive at baselinewas excluded
from the modified intention-to-treat population (group I, n = 27;
group II, n = 33; group III, n = 32). At week 48, 3.70% of subjects in
group I, 3.03% of subjects in group II and 9.38% of subjects in group III
achieved HBsAg loss. Mean HBsAg decline from baseline to week 48
was significantly greater in group III (0.85 log10IU/ml) and group II
(0.74log10 IU/ml) than in groups I (0.13log10IU/ml, respectively, p <
0.05 for all comparisons vs group I). Among the patients with 100IU/
ml < HBsAg < 1500 IU/ml at randomisation, 25% achieved HBsAg loss
and mean HBsAg declined 1.65log10 IU/ml from baseline toweek 48
in group III, displaying a significant benefit comparing with group I
(0% and 0.04log10IU/ml, respectively), while no significant difference
was found between group III and group II (6.67% and 0.61 log10IU/ml,
respectively). Besides, patients receiving combination treatment
showed a significantly higher increase in the CD56bright CD16−NK
cells proportions at week 4, patients with good response to
combination treatment exhibited a significant decline in Treg
proportions from week 12 to week 24.
Conclusion: For ETV suppressed patients, particularly those with low
serum HBsAg level, sequential combination therapy with IFN and
immunomodulators may enhance HBsAg loss and led to partial
immune restoration.
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发表于 2018-4-5 14:26